Publications by authors named "Hongyan Wang"

727 Publications

Multi-analyte High-Throughput Microplate-SERS Reader with Controllable Liquid Interfacial Arrays.

Anal Chem 2022 May 17. Epub 2022 May 17.

School of Food and Biological Engineering, Engineering Research Center of Bio-Process, Ministry of Education, Hefei University of Technology, Hefei, Anhui 230009, China.

High-throughput surface-enhanced Raman scattering (SERS) reader, especially for liquid sample testing, is of great significance and huge demand in biology, environment, and other analytical fields. Inspired by the principle of microplate reader, herein, we developed a microplate-SERS reader for semiautomatic and high-throughput assays by virtue of three-dimensional liquid interfacial arrays (LIAs). For the first time, the formation of LIA in oil-in-water state, water-in-oil state, and two-dimensional plane state is realized by operating the hydrophilicity (contact angle) of the container. Through the force analysis of LIA, the effect of organic (O) phase density on the relative position of LIA was quantified. In addition, the optimized reader offers fast and continuous semiautomatic detection of 12 samples below 10 min with great signal reproducibility (calibration with the characteristic peak of O phase as the internal standard). The isolated wells in the microplate prevent analyte cross talk, allowing accurate quantification of each sample. Multiplex analysis capability highlights that this reader has the ability of rapid identification and quantification of samples containing various analytes and concentrations. The results demonstrate high-resolution dual and triple analyte detection with fully preserved signal and Raman features of individual analytes in a mixture, which implies that it also has excellent anticounterfeiting applications. This microplate-SERS reader combines the superior advantages of the LIA, microplate, and SERS techniques to retrieve the molecular vibrational fingerprints of various chemicals in complex media.
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http://dx.doi.org/10.1021/acs.analchem.2c00252DOI Listing
May 2022

Down-regulated cylindromatosis enhances NF-κB activation and aggravates inflammation in HBV-ACLF patients.

Emerg Microbes Infect 2022 May 17:1-57. Epub 2022 May 17.

Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.

The pathogenesis of liver in patients with hepatitis B virus-associated acute - chronic liver failure (HBV-ACLF) remains largely unknown. We aimed to elucidate the molecular mechanism underlying the pathogenesis of liver in HBV-ACLF patients by using multiple approaches including transcriptome analysis. We performed transcriptomic sequencing analysis on the liver of HBV-ACLF patients (n = 6), chronic hepatitis B (n = 6), liver cirrhosis (n = 6) and normal control (n = 5), then explored the potential pathogenesis mechanism in liver specimen from another 48 subjects and further validated the molecular and cellular mechanism using THP-1 cells. RNA-sequencing data analysis indicated that, among the genes up-regulated in HBV-ACLF, genes related to inflammatory response and chemotaxis accounted for a large proportion of the total DEGs. A number of key chemokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8) and NF-ĸB pathway were identified to be robust in the liver samples from HBV-ACLF patients. Interestingly, cylindromatosis (CYLD) was found to be downregulated in the liver of HBV-ACLF patients, in line with the well-established role of CYLD in regulating most of the chemokines and pro-inflammatory cytokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8, IL-6, IL-1β) via inhibition of NF-ĸB. Indeed, knockdown of CYLD resulted in sustained activation of NF-ĸB in macrophages and enhanced chemokines and inflammatory cytokines production, which in turn enhanced chemotactic migration of neutrophil, monocyte, T lymphocytes and NK cell. In conclusions, down-regulated CYLD aggravated inflammatory cell chemotaxis through enhancing NF-κB activation in HBV-ACLF patients, thereby participating in the pathogenesis of HBV-ACLF injury.
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http://dx.doi.org/10.1080/22221751.2022.2077128DOI Listing
May 2022

Identification and validation of diagnostic and prognostic biomarkers for lung squamous cell carcinoma.

J Thorac Dis 2022 Apr;14(4):1243-1255

Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: The aim of the present study was to find diagnostic and prognostic biomarkers for lung squamous cell carcinoma (LUSC) and to validate key biomarkers .

Methods: RNA sequencing was used to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) in LUSC tissues. RNA sequencing results were validated using a published dataset. Diagnostic and prognostic values of candidate genes were evaluated by receiver-operating characteristic (ROC) curve analysis and survival analysis, respectively. To determine the effect of in LUSC, expression was knocked down in NCI-H520 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell assay were used to respectively detect the effect of on cell proliferation and migration.

Results: In total, 1,946 DEmRNAs and 428 DElncRNAs were identified in LUSC compared with normal tissues. A total of 851 DElncRNA-DEmRNA co-expression pairs were obtained. With the exception of and were upregulated in LUSC. ROC curve analysis indicated that , and could predict LUSC. Survival analysis suggested that , and had potential prognostic value for LUSC. knockdown inhibited cell proliferation and migration, and significantly reduced the expression of .

Conclusions: The findings of the present study could help determine the pathogenesis of LUSC and provide new and accurate therapeutic targets for its treatment.
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http://dx.doi.org/10.21037/jtd-22-343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096289PMC
April 2022

Assessment of Carotid Body Tumors by Superb Microvascular Imaging of Feeding Arteries During Preoperative Evaluation.

Front Surg 2022 26;9:816768. Epub 2022 Apr 26.

Department of Ultrasound, China-Japan Friendship Hospital, Beijing, China.

Purpose: Superb microvascular imaging (SMI) has led to new advances in vascular imaging applications. This study aimed to explore the blood supply and feeding arteries of carotid body tumors (CBTs) on SMI to improve the accuracy of information available to surgeons.

Methods: Twenty-six CBT lesions were subjected to color Doppler flow imaging (CDFI) and SMI and were later confirmed by pathology. The blood flow patterns and feeding arteries of the CBTs on CDFI and SMI were graded and compared.

Results: The feeding arteries of two CBT lesions, which were not visible on CDFI, were identified as the internal carotid artery (ICA) on SMI. The feeding arteries of three CBTs were judged to stem from both the ICA and the external carotid artery (ECA) (MIX) based on SMI compared to the ICA or ECA on CDFI. We classified the feeding arteries of CBTs as originating from the ICA or others (including the ECA and MIX). One hundred percent (3/3) of the CBT lesions stemming from the ICA had Adler I or Adler II blood flow patterns, and 100% (23/23) of the CBT lesions stemming from other arteries had Adler II or Adler III blood flow patterns. Higher Adler categories were assigned based on SMI than CDFI ( < 0.001).

Conclusion: SMI may be superior to CDFI in detecting the vascularity of CBTs, and SMI revealed more potential feeding arteries of CBTs than CDFI. CBTs originating from the ICA are less vascular than those originating from the ECA.
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http://dx.doi.org/10.3389/fsurg.2022.816768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090302PMC
April 2022

Correction: A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.

Mol Psychiatry 2022 May 10. Epub 2022 May 10.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering at School of Life Sciences, Children's Hospital, Fudan University, Shanghai, China.

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http://dx.doi.org/10.1038/s41380-022-01605-8DOI Listing
May 2022

Meningeal lymphatic vessels mediate neurotropic viral drainage from the central nervous system.

Nat Neurosci 2022 May 6;25(5):577-587. Epub 2022 May 6.

Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China.

Recent studies have demonstrated that brain meningeal lymphatic vessels (MLVs) act as a drainage path directly into the cervical lymph nodes (CLNs) for macromolecules contained in the cerebrospinal fluid (CSF). However, the role of MLVs during CNS viral infection remains unexplored. Here, we found that infection with several neurotropic viruses in mice promotes MLV expansion but also causes impaired MLV-mediated drainage of macromolecules. Notably, MLVs could drain virus from the CNS to CLNs. Surgical ligation of the lymph vessels or photodynamic ablation of dorsal MLVs increased neurological damage and mortality of virus-infected mice. By contrast, pretreatment with vascular endothelial growth factor C promoted expansion of functional MLVs and alleviated the effects of viral infection. Together, these data indicate that functional MLVs facilitate virus clearance, and MLVs represent a critical path for virus spreading from the CNS to the CLNs. MLV-based therapeutic strategies may thus be useful for alleviating infection-induced neurological damage.
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http://dx.doi.org/10.1038/s41593-022-01063-zDOI Listing
May 2022

Deleterious Rare Mutations of Dysregulate Sonic Hedgehog Signaling in Human Congenital Heart Disease.

Front Cardiovasc Med 2022 4;9:798033. Epub 2022 Apr 4.

NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children's Hospital, Fudan University, Shanghai, China.

The Glioma-associated oncogene (Gli) family members of zinc finger DNA-binding proteins are core effectors of Sonic hedgehog (SHH) signaling pathway. Studies in model organisms have identified that the genes play critical roles during organ development, including the heart, brain, kidneys, . Deleterious mutations in genes have previously been revealed in several human developmental disorders, but few in congenital heart disease (CHD). In this study, the mutations in genes were captured by next generation sequencing in human cohorts composed of 412 individuals with CHD and 213 ethnically matched normal controls. A total of 20 patient-specific nonsynonymous rare mutations in coding regions of human genes were identified. Functional analyses showed that c.820G> T (p.G274C) is a gain-of-function mutation, while c.878G>A (p.R293H) and c.1442T>A (p.L481X) are loss-of-function mutations. Our findings suggested that deleterious rare mutations in gene broke the balance of the SHH signaling pathway regulation and may constitute a great contribution to human CHD, which shed new light on understanding genetic mechanism of embryo cardiogenesis regulated by SHH signaling.
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http://dx.doi.org/10.3389/fcvm.2022.798033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014293PMC
April 2022

An ultrasensitive electrochemical sensing platform based on silver nanoparticle-anchored 3D reduced graphene oxide for rifampicin detection.

Analyst 2022 May 17;147(10):2156-2163. Epub 2022 May 17.

Key Laboratory of Spin Electron and Nanomaterials of Anhui Higher Education Institutes, Suzhou University, Suzhou 234000, China.

A facile strategy has been reported to anchor silver nanoparticles (Ag NPs) onto three-dimensional reduced graphene oxide (3D rGO) a green and simple method. An accurate and reliable electrochemical sensing platform based on Ag NPs/3D rGO was designed for the ultrasensitive detection of rifampicin (RIF). The morphology and features of Ag NPs/3D rGO were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Raman spectroscopy and electrochemical measurements. The interface of the modified electrode presented effective electrical activity for the analysis of RIF due to the large electrochemically active surface area and excellent electron transport ability. The sensor exhibited a good linear relationship in the range of 0.01 nM-45 μM and a low detection limit of 0.810 nM (S/N = 3). Crucially, the fabricated Ag NPs/3D rGO sensor was successfully utilized to assess RIF in human blood, drug and aquatic product samples. This sensing platform exhibited outstanding electrochemical performance for RIF detection and showed great potential application in clinical diagnosis, pharmaceutical and food-related fields.
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http://dx.doi.org/10.1039/d2an00452fDOI Listing
May 2022

Phosphorylated MED1 links transcription recycling and cancer growth.

Nucleic Acids Res 2022 05;50(8):4450-4463

Department of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.

Mediator activates RNA polymerase II (Pol II) function during transcription, but it remains unclear whether Mediator is able to travel with Pol II and regulate Pol II transcription beyond the initiation and early elongation steps. By using in vitro and in vivo transcription recycling assays, we find that human Mediator 1 (MED1), when phosphorylated at the mammal-specific threonine 1032 by cyclin-dependent kinase 9 (CDK9), dynamically moves along with Pol II throughout the transcribed genes to drive Pol II recycling after the initial round of transcription. Mechanistically, MED31 mediates the recycling of phosphorylated MED1 and Pol II, enhancing mRNA output during the transcription recycling process. Importantly, MED1 phosphorylation increases during prostate cancer progression to the lethal phase, and pharmacological inhibition of CDK9 decreases prostate tumor growth by decreasing MED1 phosphorylation and Pol II recycling. Our results reveal a novel role of MED1 in Pol II transcription and identify phosphorylated MED1 as a targetable driver of dysregulated Pol II recycling in cancer.
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http://dx.doi.org/10.1093/nar/gkac246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071494PMC
May 2022

A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.

Mol Psychiatry 2022 Apr 6. Epub 2022 Apr 6.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering at School of Life Sciences, Children's Hospital, Fudan University, Shanghai, China.

The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.
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http://dx.doi.org/10.1038/s41380-022-01539-1DOI Listing
April 2022

The Evaluation of Gait and Balance for Patients with Early Diabetic Peripheral Neuropathy: A Cross-Sectional Study.

Risk Manag Healthc Policy 2022 30;15:543-552. Epub 2022 Mar 30.

Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Objective: Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.

Methods: A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.

Results: Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p<0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p<0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p<0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p<0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p<0.05).

Conclusion: The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.

Clinical Trial Registration Number: No. ChiCTR1800019179, www.chictr.org.cn.
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http://dx.doi.org/10.2147/RMHP.S361698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977473PMC
March 2022

Comparative Analysis of Codon Bias in the Chloroplast Genomes of Theaceae Species.

Front Genet 2022 10;13:824610. Epub 2022 Mar 10.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, China.

Theaceae species are dicotyledonous angiosperms with extremely high ornamental and economic value. The chloroplast genome is traditionally used to study species evolution, expression of chloroplast genes and chloroplast transformation. Codon usage bias (CUB) analysis is beneficial for investigations of evolutionary relationships and can be used to improve gene expression efficiency in genetic transformation research. However, there are relatively few systematic studies of the CUB in the chloroplast genomes of Theaceae species. In this study, CUB and nucleotide compositions parameters were determined by the scripts written in the Perl language, CodonW 1.4.2, CU.Win2000, RStudio and SPSS 23.0. The chloroplast genome data of 40 Theaceae species were obtained to analyse the codon usage (CU) characteristics of the coding regions and the influence of the source of variation on CUB. To explore the relationship between the CUB and gene expression levels in these 40 Theaceae plastomes, the synonymous codon usage order (SCUO) and measure independent of length and composition (MILC) values were determined. Finally, phylogenetic analysis revealed the genetic evolutionary relationships among these Theaceae species. Our results showed that based on the chloroplast genomes of these 40 Theaceae species, the CUB was for codons containing A/T bases and those that ended with A/T bases. Moreover, there was great commonality in the CUB of the Theaceae species according to comparative analysis of relative synonymous codon usage (RSCU) and relative frequency of synonymous codon (RFSC): these species had 29 identical codons with bias (RSCU > 1), and there were 19 identical high-frequency codons. The CUB of Theaceae species is mainly affected by natural selection. The SCUO value of the 40 Theaceae species was 0.23 or 0.24, and the chloroplast gene expression level was moderate, according to MILC values. Additionally, we observed a positive correlation between the SCUO and MILC values, which indicated that CUB might affect gene expression. Furthermore, the phylogenetic analysis showed that the evolutionary relationships in these 40 Theaceae species were relatively conserved. A systematic study on the CUB and expression of Theaceae species provides further evidence for their evolution and phylogeny.
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http://dx.doi.org/10.3389/fgene.2022.824610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961065PMC
March 2022

Excitation-Power-Dependent Upconversion Luminescence Competition in Single β-NaYbF:Er Microcrystal Pumped at 808 nm.

Nanoscale Res Lett 2022 Mar 26;17(1):38. Epub 2022 Mar 26.

College of Advanced Interdisciplinary Studies, National University of Defense Technology, Changsha, 410073, China.

Controlling the upconversion luminescence (UCL) intensity ratio, especially pumped at 808 nm, is of fundamental importance in biological applications due to the water molecules exhibiting low absorption at this excitation wavelength. In this work, a series of β-NaYbF:Er microrods were synthesized by a simple one-pot hydrothermal method and their intense green (545 nm) and red (650 nm) UCL were experimentally investigated based on the single-particle level under the excitation of 808 nm continuous-wave (CW) laser. Interestingly, the competition between the green and red UCL can be observed in highly Yb-doped microcrystals as the excitation intensity gradually increases, which leads to the UCL color changing from green to orange. However, the microcrystals doped with low Yb concentration keep green color which is independent of the excitation power. Further investigations demonstrate that the cross-relaxation (CR) processes between Yb and Er ions result in the UCL competition.
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http://dx.doi.org/10.1186/s11671-021-03649-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964848PMC
March 2022

CCDC134 as a Prognostic-Related Biomarker in Breast Cancer Correlating With Immune Infiltrates.

Front Oncol 2022 3;12:858487. Epub 2022 Mar 3.

Department of Pharmacy, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China.

Background: The expression of Coiled-Coil Domain Containing 134(CCDC134) is up-regulated in different pan-cancer species. However, its prognostic value and correlation with immune infiltration in breast cancer are unclear. Therefore, we evaluated the prognostic role of CCDC134 in breast cancer and its correlation with immune invasion.

Methods: We downloaded the transcription profile of CCDC134 between breast cancer and normal tissues from the Cancer Genome Atlas (TCGA). CCDC134 protein expression was assessed by the Clinical Proteomic Cancer Analysis Consortium (CPTAC) and the Human Protein Atlas. Gene set enrichment analysis (GSEA) was also used for pathway analysis. Receiver operating characteristic (ROC) curve was used to differentiate breast cancer from adjacent normal tissues. Kaplan-Meier method was used to evaluate the effect of CCDC134 on survival rate. The protein-protein interaction (PPI) network is built from STRING. Function expansion analysis is performed using the ClusterProfiler package. Through tumor Immune Estimation Resource (TIMER) and tumor Immune System Interaction database (TISIDB) to determine the relationship between CCDC134 expression level and immune infiltration. CTD database is used to predict drugs that inhibit CCDC134 and PubChem database is used to determine the molecular structure of identified drugs.

Results: The expression of CCDC134 in breast cancer tissues was significantly higher than that of CCDC134 mRNA expression in adjacent normal tissues. ROC curve analysis showed that the AUC value of CCDC134 was 0.663. Kaplan-meier survival analysis showed that patients with high CCDC134 had a lower prognosis (57.27 months vs 36.96 months, P = 2.0E-6). Correlation analysis showed that CCDC134 mRNA expression was associated with tumor purity immune invasion. In addition, CTD database analysis identified abrine, Benzo A) Pyrene, bisphenol A, Soman, Sunitinib, Tetrachloroethylene, Valproic Acid as seven targeted therapy drugs that may be effective treatments for seven targeted therapeutics. It may be an effective treatment for inhibiting CCDC134.

Conclusion: In breast cancer, upregulated CCDC134 is significantly associated with lower survival and immune infiltrates invasion. Our study suggests that CCDC134 can serve as a biomarker of poor prognosis and a potential immunotherapy target in breast cancer. Seven drugs with significant potential to inhibit CCDC134 were identified.
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http://dx.doi.org/10.3389/fonc.2022.858487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927640PMC
March 2022

Downregulation of the long non-coding RNA MALAT1 in tenofovir-treated pregnant women with hepatitis B virus infection promotes immune recovery of natural killer cells via the has-miR-155-5p/HIF-1α axis.

Int Immunopharmacol 2022 Jun 17;107:108701. Epub 2022 Mar 17.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi 710061, China. Electronic address:

Background: Currently, tenofovir disoproxil fumarate (TDF) treatment in pregnant women with hepatitis B virus (HBV) infection in the second trimester of pregnancy to reduce the HBV DNA load and block the mother-to-child transmission of HBV has become a consensus. An increasing number of studies have shown that lncRNAs play an important role in immune regulation; however, there are only a few studies on how lncRNAs affect the immune function of TDF-treated pregnant women with HBV infection.

Methods: The peripheral blood of pregnant women with HBV infection was collected before and after TDF treatment for whole-transcriptome sequencing; the differential expression of lncRNA MALAT1 in PBMCs and natural killer (NK) cells was verified by qRT-PCR. ELISA and flow cytometry were used to detect the effect of MALAT1 on NK-92 cells on IFN-γ secretion. Dual-luciferase reporter, qRT-PCR, and western blot analyses were used to verify the relationship between the expression levels of MALAT1, has-miR-155-5p and HIF-1α.

Results: After TDF treatment, the MALAT1 expression in the PBMCs of pregnant women with HBV infection, especially in NK cells, was significantly reduced. MALAT1 overexpression decreased IFN-γ secretion in NK-92 cells, while IFN-γ secretion increased after MALAT1 knockdown. Mechanistically, we identified MALAT1 as a competitive endogenous RNA that regulates HIF-1α expression by sponging has-miR-155-5p. Low HIF-1α expression resulted in increased IFNG expression in, and IFN-γ secretion by, NK cells.

Conclusions: Thus, MALAT1 may play an important role in NK cell-mediated immunity in TDF-treated pregnant women with HBV infection by regulating the has-miR-155-5p/HIF-1α axis.
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http://dx.doi.org/10.1016/j.intimp.2022.108701DOI Listing
June 2022

Iodide etching for one-step quantitative assay of the number of DNA molecules capped on gold nanoparticles.

Anal Methods 2022 03 24;14(12):1232-1238. Epub 2022 Mar 24.

School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.

Developing a direct method to easily quantify the number of DNA capped on gold nanoparticles (GNPs) is of great significance. Herein, we found that the high concentration of iodine ion (I) can not only replace the ligands on the surface of GNPs but can also completely etch the particles by virtue of its strong reducibility. According to this finding, a mild, cost-effective, environment-friendly, and non-toxic strategy was constructed to directly and accurately estimate the amount of DNA coupled on GNPs. Due to nanometal surface energy transfer (NSET) that happened between the DNA-FAM donor and the GNPs receptor, the fluorescence was quenched; after incubating with the etching reagent 6 M I, the recuperative fluorescence was detected directly. This method can easily estimate the number of DNA attached on the GNPs surface by one step. In a nutshell, it is a smart strategy to apply iodide etching for DNA quantification on the surface of GNPs, which breaks through the drawbacks of traditional DNA quantification strategies such as pollution, being expensive and even dangerous. This strategy takes a solid step forward for the refinement and optimization of DNA quantification and can also be more effective in detecting the number of other molecules capped on the GNPs surface, indicating that the iodide etching method is greatly helpful in bio-detection assays and nanoparticle-based therapeutics.
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http://dx.doi.org/10.1039/d1ay02212aDOI Listing
March 2022

Adjunctive antidepressants for the acute treatment of bipolar depression: A systematic review and meta-analysis.

Psychiatry Res 2022 05 22;311:114468. Epub 2022 Feb 22.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China; CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China; Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: The depressive phase of bipolar disorder causes significant functional impairment and disease burden. The efficacy and safety of antidepressants in the treatment of bipolar depression has long been a subject of debate.

Aims: To synthesize evidence of the effectiveness, risk of mood switching, and tolerability of adjunctive antidepressants in acute bipolar depression compared to using mood stabilizers or antipsychotics alone.

Method: Multiple databases were searched for randomized controlled trials, including open label and double-blinded, for patients ages 18 or older with acute bipolar depression, comparing efficacy and adverse events in those who used adjunctive antidepressants versus without. Risk of bias and outcomes were assessed using the Cochrane Risk of Bias Tool. This study has PROSPERO registration CRD42016037701.

Results: Nineteen studies met inclusion criteria. Adjunctive antidepressants showed no significant effect on improving response rate (RR=1.10, 95%CI: 0.98-1.23). Subgroup analysis showed that adjunctive antidepressants with antipsychotics had a small but significantly better response rate compared to antipsychotics alone, which was not seen with adjunctive antidepressants with mood stabilizers. However, that finding was limited by studies predominantly using olanzapine as the antipsychotic medication. Adjunctive antidepressants had no clinically significant impact (but a small statistically significant impact) on improving depressive symptoms (SMD=-0.13, 95%CI: -0.24 to -0.02). There was no association with increased mood switch (RR=0.97, 95%CI: 0.68-1.39) and there was an association with lower dropout due to inefficacy (RR=0.66, 95%CI: 0.45∼0.98).

Conclusions: There is no evidence of adjunctive antidepressants clinically improving response rate or depressive symptoms for acute bipolar depression. They are well tolerated, without increasing the risk of short-term mood switch.
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http://dx.doi.org/10.1016/j.psychres.2022.114468DOI Listing
May 2022

sp. Strain IAE Dihaloeliminates 1,1,2-Trichloroethane and 1,2-Dichloroethane.

Environ Sci Technol 2022 03 3;56(6):3430-3440. Epub 2022 Mar 3.

Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China.

Chlorinated ethanes, including 1,2-dichloroethane (1,2-DCA) and 1,1,2-trichloroethane (1,1,2-TCA), are widespread groundwater contaminants. Enrichment cultures XR and XR derived from river sediment dihaloeliminated 1,2-DCA to ethene and 1,1,2-TCA to vinyl chloride (VC), respectively. The XR culture subsequently converted VC to ethene hydrogenolysis. Microbial community profiling demonstrated the enrichment of 16S rRNA gene sequences in both the XR and XR cultures, and () sequences were only detected in the ethene-producing XR culture. The presence of a novel population, designated as sp. strain IAE, was identified by the 16S rRNA gene-targeted polymerase chain reaction and Sanger sequencing. Time-resolved population dynamics attributed the dihaloelimination activity to strain IAE, which attained the growth yields of 0.93 ± 0.06 × 10 and 1.18 ± 0.14 × 10 cells per μmol Cl released with 1,2-DCA and 1,1,2-TCA as electron acceptors, respectively. In contrast, growth only occurred during VC-to-ethene hydrogenolysis. Our findings discover a sp. strain capable of respiring multiple chlorinated ethanes and demonstrate the involvement of a broader diversity of organohalide-respiring bacteria in the detoxification of 1,2-DCA and 1,1,2-TCA.
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http://dx.doi.org/10.1021/acs.est.1c05952DOI Listing
March 2022

Waste-converted nitrogen and fluorine co-doped porous carbon nanosheets for high performance supercapacitor with ionic liquid electrolyte.

J Colloid Interface Sci 2022 Jun 22;616:413-421. Epub 2022 Feb 22.

Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai 200241, PR China. Electronic address:

In this work, nitrogen and fluorine co-doped porous carbon nanosheets (NFPCNS) were fabricated from pharmaceutical drug residues derived from the fermentation synthesis of lincomycin hydrochloride via high-temperature pyrolysis and subsequent KOH activation without adding any nitrogen and fluorine reagents. The obtained NFPCNS exhibits an optimized integration of three dimensional interconnected nanosheet structure, large specific surface area of 2912 m g, hierarchical porous structure with large mesopore proportion (S/S = 151.5%, V/V = 248.2%) and high level heteroatom content (13.2 at.% O, 4.3 at.% N and 1.0 at.% F). Therefore, NFPCNS based supercapacitors using 1-ethyl-3-methylimidazolium tetrafluoroborate electrolyte exhibit an excellent gravimetric capacitance of 296F g at 1 A g, good rate capability of 65% at 20 A g and high energy density of 125 Wh kg. Furthermore, an ultra-high energy density of 173 Wh kg and a long cycling life with 93% capacitance retention after 2000 cycles has been achieved by NFPCNS based supercapacitors with 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide electrolyte. NFPCNS should be a green and efficient electrode materials for next-generation high-energy supercapacitors.
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http://dx.doi.org/10.1016/j.jcis.2022.02.087DOI Listing
June 2022

AKT2 reduces IFNβ1 production to modulate antiviral responses and systemic lupus erythematosus.

EMBO J 2022 03 22;41(6):e108016. Epub 2022 Feb 22.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Interferon regulatory factor 3 (IRF3)-induced type I interferon (I-IFN) production plays key roles in both antiviral and autoimmune responses. IRF3 phosphorylation, dimerization, and nuclear localization are needed for its activation and function, but the precise regulatory mechanisms remain to be explored. Here, we show that the serine/threonine kinase AKT2 interacts with IRF3 and phosphorylates it on Thr207, thereby attenuating IRF3 nuclear translocation in a 14-3-3ε-dependent manner and reducing I-IFN production. We further find that AKT2 expression is downregulated in viral-infected macrophages or in monocytes and tissue samples from systemic lupus erythematosus (SLE) patients and mouse models. Akt2-deficient mice exhibit increased I-IFN induction and reduced mortality in response to viral infection, but aggravated severity of SLE. Overexpression of AKT2 kinase-inactive or IRF3-T207A mutants in zebrafish supports that AKT2 negatively regulates I-IFN production and antiviral response in a kinase-dependent manner. This negative role of AKT2 in IRF3-induced I-IFN production suggests that AKT2 may be therapeutically targeted to differentially regulate antiviral infection and SLE.
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http://dx.doi.org/10.15252/embj.2021108016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922272PMC
March 2022

Parental folate deficiency induces birth defects in mice accompanied with increased de novo mutations.

Cell Discov 2022 Feb 22;8(1):18. Epub 2022 Feb 22.

Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.

Dietary folate deficiency (FD) is associated with the occurrence of birth defects. However, the mechanisms underlying this association remain elusive. In particular, how FD affects genome stability is unknown. To examine whether a folate-deficient diet can affect genome stability, C57BL/6 mice were maintained on a synthetic diet lacking of folic acid (FA) for two generations. F0 mice received the FD diet beginning at 3 weeks of age, and their offspring (F1) began the FD diet after weaning. Both male and female F1 mice fed the FD diet were intentionally crossed with F1 mice fed the normal diet to produce F2 mice. F2 embryos were dissected and collected at E14.5 and E18.5. The malformation ratio was significantly increased in F2 embryos fed the FD diet for two generations compared to those fed the normal diet. Whole-genome sequencing of multiple sibship with F1 males on the FD diet showed that the de novo mutation (DNM) rate in F2 embryos was three times of the reported spontaneous rate in mice. Furthermore, many DNMs observed in the F2 mice exhibited an allele ratio of 1:3 instead of 2:2, suggesting that these mutations are likely to accumulate in gamete cells as a form of mismatch in the DNA duplex. Our study indicated that FD for two generations significantly enhances DNM accumulation during meiosis, which might contribute to the increased negative birth outcomes among F2 mice. Not only maternal but also paternal FA supplementation is probably also necessary and beneficial to prevent birth defects.
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http://dx.doi.org/10.1038/s41421-021-00364-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861018PMC
February 2022

Strain-tuned mechanical, electronic, and optoelectronic properties of two-dimensional transition metal sulfides ZrS: a first-principles study.

J Mol Model 2022 Feb 18;28(3):63. Epub 2022 Feb 18.

School of Physical Science and Technology, Southwest Jiaotong University, Chengdu, 611756, People's Republic of China.

Two-dimensional semiconductor material zirconium disulfide (ZrS) monolayer is a new promising material with good prospects for nanoscale applications. Recently, a new zirconium disulfide (ZrS) monolayer with a space group of 59_Pmmn has been successfully predicted. Using first-principles calculations, this new monolayer ZrS structure is obtained with stable indirect bandgaps of 0.65 eV and 1.46 eV at the DFT-PBE (HSE06) functional levels, respectively. Strain engineering studies on the ZrS monolayer show effective bandgap modulation. The bandgap shows a nearly linear regularity from narrow to wide under strain (ranged from - 6 to + 8%). Young's modulus of elasticity of ZrS along the tensile directions (x-axis and y-axis) is 83.63 (N/m) and 63.61 (N/m) with Poisson's ratios of 0.09 and 0.07, respectively. The results of carrier mobility show that the electron mobility along the y-axis can reach 1.32 × 10 cm V s. Besides, the order of magnitude of the light absorption coefficient in the ultraviolet spectral region is calculated to reach 2.0 × 10 cm for ZrS monolayers. Moreover, the bandgap and band edge position of Pmmn-ZrS can satisfy the redox potentials of photocatalytic water splitting by strain regulating. The results indicate that the new two-dimensional Pmmn-ZrS monolayer is a potential material for photovoltaic devices and photocatalytic water decomposition.
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http://dx.doi.org/10.1007/s00894-022-05052-8DOI Listing
February 2022

Development and validation of a predictive model for urinary incontinence postpartum: a prospective longitudinal study.

Int Urogynecol J 2022 Feb 19. Epub 2022 Feb 19.

Women's Hospital, School of Medicine Zhejiang University, No.1 Xue Shi Road, Zhejiang Province, 310006, Hangzhou, China.

Introduction And Hypothesis: Urinary incontinence is a common and burdensome problem amongst women. Although it can be prevented, little progress has been made. Identifying individuals at risk remains the key to the prevention of urinary incontinence.

Methods: Eligible women were enrolled in the obstetric wards of a tertiary maternity hospital in 2020. Urinary incontinence was measured using a well-accepted questionnaire. Logistic regression with a backward stepwise process was used for predictor selection. The discrimination and calibration of the nomogram were measured using the area under the ROC curve (AUC), Hosmer-Lemeshow test and calibration curve respectively. Bootstrapping procedure with 1000 resamples was used for internal validity. A temporal split (7:3) was made and data collected from the later period were used for temporal validation.

Results: Seven predictors including birth mode, urinary incontinence before and during pregnancy, place of residence, feeding pattern, parity, and age at first birth remained in the final model. The AUC was 0.757 (95% CI: 0.72-0.80) and 0.759 (95% CI: 0.70-0.82) in the derivation and validation cohorts respectively. No significant differences were detected in the Hosmer-Lemeshow test and calibration curve in both cohorts.

Conclusions: The nomogram proved to be a convenient and reliable tool in the clinical setting for risk assessment of postpartum incontinence, which can be applied during pregnancy and the postnatal period for individual risk estimates of postpartum incontinence.
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http://dx.doi.org/10.1007/s00192-022-05105-9DOI Listing
February 2022

Re-visiting the principles of apicobasal polarity in Drosophila neural stem cells.

Dev Biol 2022 04 16;484:57-62. Epub 2022 Feb 16.

Neuroscience & Behavioral Disorders Programme, Duke-NUS Medical School, 8 College Road, 169857, Singapore; Dept. of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Integrative Sciences and Engineering Programme, National University of Singapore, 28 Medical Drive, 117456, Singapore. Electronic address:

The ability of stem cells to divide asymmetrically is crucial for cell-type diversity and tissue homeostasis. Drosophila neural stem cells, also knowns as neuroblasts, utilize asymmetric cell division to self-renew and give rise to differentiated daughter cells. Drosophila neuroblasts relies on the polarized protein complexes on the apical and basal cortex to govern cell polarity and asymmetry. Here, we review recent advances in our understanding of the neuroblast polarity focusing on how actin cytoskeleton, phosphoinositide lipids and liquid-liquid phase separation regulate the asymmetric cell division of Drosophila neuroblasts.
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http://dx.doi.org/10.1016/j.ydbio.2022.02.006DOI Listing
April 2022

Role of fibulin-1 gene promoter methylation in the carcinogenesis and development of tongue squamous cell carcinoma.

Oral Surg Oral Med Oral Pathol Oral Radiol 2022 04 14;133(4):432-440. Epub 2021 Oct 14.

Department of Stomatology, Daqing Oilfield General Hospital, Daqing, China.

Objective: Recently, fibulin-1 (FBLN1) has been shown to be downregulated in various cancers via promoter hypermethylation. Our study aimed to determine the expression and methylation status of FBLN1 in tongue squamous cell carcinoma (TSCC) tissues and cells.

Methods: Methylation-specific polymerase chain reaction was implemented to detect the methylation status of the FBLN1 gene in TSCC tissues and Western blot analysis was used to detect the expression of FBLN1 protein. The human TSCC cell lines CAL27 and SCC9 were cultured in vitro and treated with 5-aza-deoxycytidine (5-Aza-dC). CCK-8, colony formation, and Transwell assays were performed to test TSCC cell proliferation, migration, and invasion following 5-Aza-dC treatment or overexpression of FBLN1, which was further verified in in vivo experiments.

Results: FBLN1 was hypermethylated and the protein expression was reduced in TSCC tissues. After human TSCC cell lines (CAL27 and SCC9) were treated with 5-Aza-dC or overexpressed FBLN1, FBLN1 expression was upregulated and the TSCC cell proliferation, migration, and invasion abilities were suppressed. In vivo experiments further showed that demethylation or overexpression of FBLN1 slowed tumor growth in nude mice.

Conclusion: This study demonstrated that 5-Aza-dC treatment or overexpression of FBLN1 inhibited the growth of human TSCC.
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http://dx.doi.org/10.1016/j.oooo.2021.10.006DOI Listing
April 2022

Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice.

PLoS One 2022 3;17(2):e0255710. Epub 2022 Feb 3.

Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Modestly increased expression of transactive response DNA binding protein (TDP-43) gene have been reported in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neuromuscular diseases. However, whether this modest elevation triggers neurodegeneration is not known. Although high levels of TDP-43 overexpression have been modeled in mice and shown to cause early death, models with low-level overexpression that mimic the human condition have not been established. In this study, transgenic mice overexpressing wild type TDP-43 at less than 60% above the endogenous CNS levels were constructed, and their phenotypes analyzed by a variety of techniques, including biochemical, molecular, histological, behavioral techniques and electromyography. The TDP-43 transgene was expressed in neurons, astrocytes, and oligodendrocytes in the cortex and predominantly in astrocytes and oligodendrocytes in the spinal cord. The mice developed a reproducible progressive weakness ending in paralysis in mid-life. Detailed analysis showed ~30% loss of large pyramidal neurons in the layer V motor cortex; in the spinal cord, severe demyelination was accompanied by oligodendrocyte injury, protein aggregation, astrogliosis and microgliosis, and elevation of neuroinflammation. Surprisingly, there was no loss of lower motor neurons in the lumbar spinal cord despite the complete paralysis of the hindlimbs. However, denervation was detected at the neuromuscular junction. These results demonstrate that low-level TDP-43 overexpression can cause diverse aspects of ALS, including late-onset and progressive motor dysfunction, neuroinflammation, and neurodegeneration. Our findings suggest that persistent modest elevations in TDP-43 expression can lead to ALS and other neurological disorders involving TDP-43 proteinopathy. Because of the predictable and progressive clinical paralytic phenotype, this transgenic mouse model will be useful in preclinical trial of therapeutics targeting neurological disorders associated with elevated levels of TDP-43.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255710PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812852PMC
February 2022

The impact and mechanisms of the Shanghai pilot free-trade zone on the green total factor productivity of the Yangtze River Delta Urban Agglomeration.

Environ Sci Pollut Res Int 2022 Jan 27. Epub 2022 Jan 27.

School of Economics and Management, Shandong Jiaotong University, Jinan Shandong, 250358, China.

Free-trade zones are highlands of regional development that have a radiating effect on surrounding cities. This paper uses Yangtze River Delta Urban Agglomeration (YRDUA) data from 2003 to 2018, to examine the impact of the China (Shanghai) pilot free-trade zone (SPFTZ) on green total factor productivity (GTFP) in the YRDUA. It uses the regression discontinuity (RD) method and analyzes the influence mechanism with the help of the mediating effect model. The paper presents the following major findings. The establishment of the SPFTZ significantly promoted GTFP in the YRDUA, with technological progress being the main driving force. An analysis using the mediating effect model found that financial efficiency and industrial structure upgrading play a complete mediating role in GTFP growth in the YRDUA. Therefore, the SPFTZ should make use of its policy advantages, take full advantage of the effect of the green growth pole, and promote green mutual development with the YRDUA.
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http://dx.doi.org/10.1007/s11356-021-17758-yDOI Listing
January 2022

Synergistic Effects of Bacillus amyloliquefaciens SDTB009 and Difenoconazole on Fusarium Wilt of Tomato.

Plant Dis 2022 Jan 25. Epub 2022 Jan 25.

Chinese Academy of Agricultural Sciences Tobacco Research Institute, 243822, Keyuan 4TH Road Laoshan District, Qingdao, Shandong, China, 266010;

Fusarium wilt is a destructive and widespread disease of tomatoes in China, and currently, there are no effective and environmentally friendly control measures. Combining biological control agents with fungicides has become an executable method for disease control. Here, Bacillus amyloliquefaciens SDTB009 showed excellent in vitro antagonistic activity against Fusarium oxysporum and tolerance to high concentrations of difenoconazole (200 mg/L) in vitro. The combination of SDTB009 and difenoconazole exhibited more effectiveness in mycelial growth inhibition than either treatment alone. Compared with that in the SDTB009 bulk solution in vitro (5.22 g/L), surfactin titer reached 7.15 g/L in the 100 mg/L difenoconazole-containing medium. Interestingly, the upregulation of twenty genes in the surfactin biosynthesis pathway from 2-fold to 4-fold was observed, explaining the synergistic effect. The SDTB009 combined with varying concentrations of difenoconazole (60, 120, 150 g a.i./ha) showed a synergistic effect in two consecutive years of field trials. These results show that the integration of difenoconazole with the biocontrol agent B. amyloliquefaciens SDTB009 synergistically increases the control efficacy of the fungicide against tomato Fusarium wilt.
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http://dx.doi.org/10.1094/PDIS-12-21-2650-REDOI Listing
January 2022

Tianma Formula Alleviates Dementia via ACER2-Mediated Sphingolipid Signaling Pathway Involving A.

Evid Based Complement Alternat Med 2021 4;2021:6029237. Epub 2021 Aug 4.

School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.

Objective: To reveal the molecular mechanism of the antagonistic effect of traditional Chinese medicine Tianma formula (TF) on dementia including vascular dementia (VaD) and Alzheimer's disease (AD) and to provide a scientific basis for the study of traditional Chinese medicine for prevention and treatment of dementia.

Method: The TF was derived from the concerted application of traditional Chinese medicine. We detected the pharmacological effect of TF in VaD rats. The molecular mechanism of TF was examined by APP/PS1 mice in vivo, () in vitro, ELISA, pathological assay via HE staining, and transcriptome. Based on RNA-seq analysis in VaD rats, the differentially expressed genes (DEGs) were identified and then verified by quantitative PCR (qPCR) and ELISA. The molecular mechanisms of TF on dementia were further confirmed by network pharmacology and molecular docking finally.

Results: The Morris water maze showed that TF could improve the cognitive memory function of the VaD rats. The ELISA and histological analysis suggested that TF could protect the hippocampus via reducing tau and IL-6 levels and increasing SYN expression. Meanwhile, it could protect the neurological function by alleviating A deposition in APP/PS1 mice and . In the RNA-seq analysis, 3 sphingolipid metabolism pathway-related genes, ADORA3, FCER1G, and ACER2, and another 5 nerve-related genes in 45 key DEGs were identified, so it indicated that the protection mechanism of TF was mainly associated with the sphingolipid metabolism pathway. In the qPCR assay, compared with the model group, the mRNA expressions of the 8 genes mentioned above were upregulated, and these results were consistent with RNA-seq. The protein and mRNA levels of ACER2 were also upregulated. Also, the results of network pharmacology analysis and molecular docking were consistent with those of RNA-seq analysis.

Conclusion: TF alleviates dementia by reducing A deposition via the ACER2-mediated sphingolipid signaling pathway.
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http://dx.doi.org/10.1155/2021/6029237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357478PMC
August 2021

Role of PG0192 and PG0193 in the modulation of pro-inflammatory cytokines in macrophages in response to Porphyromonas gingivalis.

Eur J Oral Sci 2022 04 20;130(2):e12851. Epub 2022 Jan 20.

Department of Periodontology, School of Stomatology, China Medical University, Shenyang, Liaoning Province, China.

Porphyromonas gingivalis is the main pathogen of chronic periodontitis. However, the specific mechanisms through which P. gingivalis induces immune and inflammatory responses in periodontitis have not been completely elucidated. In this study, we investigated the effects of the P. gingivalis outer membrane protein OmpH (encoded by PG0192 and PG0193) on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression in macrophages to assess the pro-inflammatory cytokine responses. A PG0192-PG0193 deletion mutant strain and a com△PG0192-0193 strain were constructed. Furthermore, rOmpH-1 and rOmpH-2 encoded by PG0192 and PG0193, respectively, were cloned, expressed, and purified for subsequent experiments. Notably, the expression of IL-6 and TNF-α at mRNA and protein levels was downregulated upon treatment of macrophages with the PG0192-PG0193 deletion mutant strain, whereas treatment of macrophages with P. gingivalis W83 co-incubated with rOmpH-1 or rOmpH-2 upregulated IL-6 and TNF-α mRNA levels. The addition of C5aR antagonist blocked this induction. Overall, our findings provided important insights into the roles of PG0192 and PG0193 for promoting IL-6 and TNF-α expression in macrophages exposed to P. gingivalis and revealed the involvement of C5aR in the pro-inflammatory response.
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http://dx.doi.org/10.1111/eos.12851DOI Listing
April 2022
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